Bicyclo nonane conformational behavior

C. Influence of 1,5- and 9-Substituents on the Conformational Behavior of Bicyclo[3.3.1]nonanes... 

Significant progress in conformational studies of bicyclo [3.3.1] nonanes in the past two decades have revealed the main conformational features of carbocyclic compounds bearing different substituents, including the ways in which both chair-boat and boat-boat conformations could be stabilized. The conformational behavior of some heterobicyclo[3.3.1]nonanes was interpreted in terms of conformational effects (8). Naturally occurring compounds that include the bicyclo[3.3.1]nonane moiety in their structure have also been studied extensively (9-15). 

In the present chapter, the basic principles of the conformational analysis of substituted bicyclo[3.3.1]nonanes and their hetero analogs are considered. These principles are illustrated with experimental and computational data with attention concentrated on those results believed most important to the understanding of the conformational behavior of bicyclo[3.3.1] nonanes. Some results previously reviewed in references 1 and 2 are not discussed here. Conformational studies of polycyclic compounds that incorporate the bicyclo [3.3.1] nonane skeleton as part of their structure are generally beyond the scope of this chapter. 

The factors thus far considered determine the conformational behavior of alkyl-substituted bicyclo[3.3.1]nonanes and their hetero analogs in molecules in which the interaction of heteroatoms is approximately the same in different conformations. In other cases, the interaction of heteroatoms or functional groups, especially at 3-, 7-, and 9-positions, may lead to significant deviations from that of the conformational behavior of alkyl-substituted carbocyclic analogs (vide infra). Thus, not only the dipole-dipole interactions but also lone pair interactions must be taken into account. In molecules bearing several substituents and heteroatoms in different positions, a very careful analysis is necessary in making predictions since different factors can cause opposite effects and the overall conformational behavior will be determined by their balance. 

The substituents at the endo-3 and endo-1 positions have a dramatic influence on the conformational behavior of bicyclo[3.3.1]nonanes and determine in many cases the preference for CC, CB, or BB conformations. 

The introduction of 1- and 5-substituents usually does not influence significantly the conformational behavior of bicyclo[3.3.1]nonanes. Molecular mechanics calculations (39) show that the presence of two methyl groups at the 1 - and 5-positions (compound 64) leads to some decrease (of approximately 0.03 A) of the C3 - C7 distance as compared with bicyclo[3.3.1]nonane itself. The substituents in these positions decrease the possibility of the wings flattening and could somewhat increase the interaction between substituent groups or lone electron pairs at endo-3 and endo-1 positions. 

Comparatively few data are available on the conformational behavior of bicyclo[3.3.1]nonanes devoid of skeletal heteroatoms and containing substituents at the 2-, 4-, 6-, or 8-positions. Compounds containing an exo-2-chlorine (compound 82, X-ray diffraction data (61)), two exo-methoxy-groups or one exo-acetoxy and one exo-methyl-group at the 2- and 4-positions (compounds 83 (62,63) and 84 (64), respectively, 1H- and 13C-NMR... 

In this section we have described the conformational behavior only of compounds containing the carbocyclic bicyclo[3.3.1]nonane skeleton their behavior is governed mainly by steric interactions. 

The influence of substituents on the conformational behavior of 3-aza-bicyclo[3.3.1]nonanes is generally similar to that observed for carbocyclic analogs. 13C-NMR data on 41 compounds of types 120-123 demonstrate a... 

Specific interactions of heteroatoms can strongly affect the conformational behavior. Interesting results have been obtained for a series of 3,7,9-trihetero-bicyclo[3.3.1]nonanes. For compounds 213 and 214 with oxygen and sulfur atoms at the 3- and 7-positions, the CC conformation is the most stable one both in the solid state and in solution (87, 156-158). In contrast, the presence of two sulfur atoms, or one sulfur and one selenium atom, at the 3- and 7-positions of compounds 215 and 216 destabilizes the chair-chair conformation (87,156,159,160). This phenomenon was explained by the destabilizing... 

The data considered here demonstrate that, despite occasionally unusual conformational behavior, the preferred conformation of the bicyclo[3.3.1]nonane system can be predicted following the analysis of intramolecular interactions and a comparison with the conformational behavior of molecules already described. In many cases, the preferred... 

The conformational analysis of bicyclo[3.3.1]nonanes continues to develop. Despite the publication of a great many experimental and calculational results, as evidenced in this chapter, at present, the conformational behavior of many comparatively simple structures has not yet been investigated. 

In the third chapter, Nikolai S. Zefirov and Vladimir A. Palyulin have summarized the conformational behavior of bicyclo[3.3.1]nonanes and their hetero analogs. This review reflects a thoroughly modern viewpoint in which calculations, x-ray crystallographic results and spectroscopic data all are brought to bear on a polycyclic molecular framework that is able to support several relatively stable conformations including some in which boats figure prominently. 

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